Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05-HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at HLA-DRbeta1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.
Autoimmunity ; Exome ; Genetic Predisposition to Disease ; Genotype* ; Haplotypes ; Hemoglobin A, Glycosylated ; Histidine ; HLA Antigens ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Leukocytes ; Risk Factors

Objectives: . Our research group has previously demonstrated that hearing loss might be a risk factor for synaptic loss within the hippocampus and impairment of cognition using an animal model of Alzheimer disease. In this study, after inducing hearing loss in a rat model of Alzheimer disease, the associations of various microRNAs (miRNAs) with cognitive impairment were investigated. Methods: . Rats were divided randomly into two experimental groups: the control group, which underwent sham surgery and subthreshold amyloid-β infusion and the deaf group, which underwent bilateral cochlear ablation and subthreshold amyloid-β infusion. All rats completed several cognitive function assessments 11 weeks after surgery, including the object-in-place task (OPT), the novel object recognition task (NOR), the object location task (OLT), and the Y-maze test. After the rats completed these tests, hippocampus tissue samples were assessed using miRNA microarrays. Candidate miRNAs were selected based on the results and then validated with quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analyses. Results: . The deaf group showed considerably lower scores on the OPT, OLT, and Y-maze test than the control group. The microarray analysis revealed that miR-29b-3p, -30e-5p, -153-3p, -376a-3p, -598-3p, -652-5p, and -873-3p were candidate miRNAs, and qRT-PCR showed significantly higher levels of miR-376a-3p and miR-598-3p in the deaf group. Conclusion . These results indicate that miR-376a-3p and miR-598-3p were related to cognitive impairment after hearing loss.